Immunomodulation of Salivary Gland Function Due to Cancer Therapy

Overview

Journal Oral Dis

Specialty Dentistry

Date 2024 May 2

PMID 38696474

Authors

Ana C Costa-da-Silva

Carlos U Villapudua

Matthew P Hoffman

Marit H Aure

Affiliations

Soon will be listed here.

Abstract

Functional salivary glands (SG) are essential for maintaining oral health, and salivary dysfunction is a persistent major clinical challenge. Several cancer therapies also have off-target effects leading to SG dysfunction. Recent advances highlight the role of SG immune populations in homeostasis, dysfunction and gland regeneration. Here, we review what is known about SG immune populations during development and postnatal homeostasis. We summarize recent findings of immune cell involvement in SG dysfunction following cancer treatments such as irradiation (IR) for head and neck cancers, immune transplant leading to graft-versus-host-disease (GVHD) and immune checkpoint inhibitor (ICI) treatment. The role of immune cells in SG in both homeostasis and disease, is an emerging field of research that may provide important clues to organ dysfunction and lead to novel therapeutic targets.

References

Caldeira-Dantas S, Furmanak T, Smith C, Quinn M, Teos L, Ertel A . The Chemokine Receptor CXCR3 Promotes CD8 T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection. J Immunol. 2017; 200(3):1133-1145. PMC: 5780235. DOI: 10.4049/jimmunol.1701272. View

Distler J, Gyorfi A, Ramanujam M, Whitfield M, Konigshoff M, Lafyatis R . Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol. 2019; 15(12):705-730. DOI: 10.1038/s41584-019-0322-7. View

Teymoortash A, Simolka N, Schrader C, Tiemann M, Werner J . Lymphocyte subsets in irradiation-induced sialadenitis of the submandibular gland. Histopathology. 2005; 47(5):493-500. DOI: 10.1111/j.1365-2559.2005.02256.x. View

Chia S, Kapoor S, Carvalho C, Bajenoff M, Gentek R . Mast cell ontogeny: From fetal development to life-long health and disease. Immunol Rev. 2023; 315(1):31-53. PMC: 10952628. DOI: 10.1111/imr.13191. View

Soares A, Faria P, Magna L, Correa M, de Sousa C, Almeida O . Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients. J Oral Pathol Med. 2005; 34(6):368-73. DOI: 10.1111/j.1600-0714.2005.00322.x. View

Thom J, Weber T, Walton S, Torti N, Oxenius A . The Salivary Gland Acts as a Sink for Tissue-Resident Memory CD8(+) T Cells, Facilitating Protection from Local Cytomegalovirus Infection. Cell Rep. 2015; 13(6):1125-1136. DOI: 10.1016/j.celrep.2015.09.082. View

Lombaert I, Brunsting J, Wierenga P, Kampinga H, de Haan G, Coppes R . Cytokine treatment improves parenchymal and vascular damage of salivary glands after irradiation. Clin Cancer Res. 2008; 14(23):7741-50. DOI: 10.1158/1078-0432.CCR-08-1449. View

Rheinheimer B, Pasquale M, Limesand K, Hoffman M, Chibly A . Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands. iScience. 2023; 26(5):106660. PMC: 10165028. DOI: 10.1016/j.isci.2023.106660. View

Formenti S, Demaria S . Systemic effects of local radiotherapy. Lancet Oncol. 2009; 10(7):718-26. PMC: 2782943. DOI: 10.1016/S1470-2045(09)70082-8. View

10.

Zhao Q, Zhang L, Hai B, Wang J, Baetge C, Deveau M . Transient Activation of the Hedgehog-Gli Pathway Rescues Radiotherapy-Induced Dry Mouth via Recovering Salivary Gland Resident Macrophages. Cancer Res. 2020; 80(24):5531-5542. PMC: 7744395. DOI: 10.1158/0008-5472.CAN-20-0503. View

11.

Hauser B, Aure M, Kelly M, Hoffman M, Chibly A . Generation of a Single-Cell RNAseq Atlas of Murine Salivary Gland Development. iScience. 2020; 23(12):101838. PMC: 7718488. DOI: 10.1016/j.isci.2020.101838. View

12.

Gyurkocza B, Sandmaier B . Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014; 124(3):344-53. PMC: 4102707. DOI: 10.1182/blood-2014-02-514778. View

13.

Weng P, Aure M, Maruyama T, Ovitt C . Limited Regeneration of Adult Salivary Glands after Severe Injury Involves Cellular Plasticity. Cell Rep. 2018; 24(6):1464-1470.e3. PMC: 6350767. DOI: 10.1016/j.celrep.2018.07.016. View

14.

Han P, Lakshminarayanan P, Jiang W, Shpitser I, Hui X, Lee S . Dose/Volume histogram patterns in Salivary Gland subvolumes influence xerostomia injury and recovery. Sci Rep. 2019; 9(1):3616. PMC: 6401158. DOI: 10.1038/s41598-019-40228-y. View

15.

Mays J, Fassil H, Edwards D, Pavletic S, Bassim C . Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis. 2012; 19(4):327-46. PMC: 3561479. DOI: 10.1111/odi.12028. View

16.

Zhang C, Xiang B . The underlying mechanisms and strategies of DNA damage and repair in radiation sialadenitis. Oral Dis. 2021; 29(3):990-995. DOI: 10.1111/odi.14078. View

17.

Cortez V, Fuchs A, Cella M, Gilfillan S, Colonna M . Cutting edge: Salivary gland NK cells develop independently of Nfil3 in steady-state. J Immunol. 2014; 192(10):4487-91. DOI: 10.4049/jimmunol.1303469. View

18.

Epstein J, Thariat J, Bensadoun R, Barasch A, Murphy B, Kolnick L . Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012; 62(6):400-22. DOI: 10.3322/caac.21157. View

19.

Guermonprez P, Gerber-Ferder Y, Vaivode K, Bourdely P, Helft J . Origin and development of classical dendritic cells. Int Rev Cell Mol Biol. 2019; 349:1-54. DOI: 10.1016/bs.ircmb.2019.08.002. View

20.

Cortez V, Cervantes-Barragan L, Robinette M, Bando J, Wang Y, Geiger T . Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands. Immunity. 2016; 44(5):1127-39. PMC: 5114145. DOI: 10.1016/j.immuni.2016.03.007. View